Wound healing is a complex process. In normal skin, the epidermis and dermis exists in steady state equilibrium, forming a barrier against the external environment. Normal wound healing processes can be classified into three stages namely the inflammatory, proliferative and maturation phases. The inflammatory phase typically lasts 0-2 days and involves an orderly recruitment of cells to the wound area. This is followed by the 2-6 day proliferative phase, in which fibroblasts, keratinocytes and other cells in the wound bed begin to actively proliferate to close the wound. During the first phase of tissue repair, an acute inflammatory response with cellular migration occurs. Neutrophils predominate for the first 24-48 hours and macrophages become active by the third day. The neutrophils and macrophages phagocytose and digest pathologic organisms and tissue debris. The maturation phase follows the proliferative phase, peaking at 21 days.
Growth factors are known to play an important role in the wound healing process and are involved in a number of critical cellular processes including cell proliferation, adhesion, morphologic appearance, differentiation, migration, inflammatory responses, angiogenesis, and cell death.
Under appropriate conditions, fibroblasts secret collagens, glycosaminoglycans, reticular and elastic fibers, glycoproteins found in the extracellular matrix and cytokine thymic stromal lymphoprotein or cytokine TSLP which are beneficial to wound or burn treatment. It has been shown that tissue damage stimulates fibrocytes and inducing cellular division. Fibroblasts synthesize the extracellular matrix and collagen in animal tissues and play a critical role in wound healing. Keratinocytes constitute 90% of the cells found in the epidermis. The primary function of keratinocytes is the formation of a barrier against environmental damage such as pathogens (bacteria, fungi, parasites, viruses), heat, UV radiation and water loss. Once pathogens start to invade the upper layers of the epidermis, keratinocytes react with the production of proinflammatory mediators and in particular chemokines such as CXCL10, CCL2 which attract leukocytes to the site of pathogen invasion.
There are currently no dermatologic or cosmetic compositions whereby cell culture conditions yield a cellular population predominated by keratinocytes and fibroblasts that secrete such high concentrations of beneficial proteins and other compounds with therapeutic properties.